Directing group assisted meta-hydroxylation by C–H activation

Abstract

The first template assisted meta-hydroxylation strategy and its use in the synthesis of resveratrol precursor and QR-activity inducer with detailed experimental and in-silico mechanistic understanding.

Accessing Remote meta‐ and para‐C(sp2)−H Bonds with Covalently Attached Directing Groups

“…[31] We demonstrated the feasibilty of the procedure for performing meta-CÀHa cetoxylation and au nique meta-CÀHh ydroxylation independently.T he use of PhI(OAc) 2 in the presence of apalladium catalyst and an amino acid ligand in HFIP solvent led to meta-acetoxylation in high selectivity (meta/others, 26:1; 78 a-d). Basic hydrolysis at room temperature afforded diacids in high yields (98 %).…”

“…Thep otential of this procedure was demonstrated by sequential ortho-and meta-olefination of phenethylamine derivatives (31)(32)(33)(34)(35)(36). Finally,the directing group was removed under acid hydrolysis to afford meta-substituted phenylethylamine 37.…”

Transition-metal-catalyzed synthesis of phenols and aryl thiols

“…In 2016, Sunoj and co-workers disclosed the first meta -hydroxylation of arenes using a tethered -CN directing group [68]. The conversion proceeded at 70 °C in hexafluoro-2-propanol (HFIP) in the presence of Pd(OAc) 2 , PhI(TFA) 2 and For-Gly-OH (Scheme 39).…”

Rhodium‐Catalyzed meta‐C−H Functionalization of Arenes

“…Several transition metals can effectively catalyze selective C À Hfunctionalization reactions with the assistance of directing groups (DGs). [4] In these cases,anitrilecontaining template assists the palladium center to activate remote meta-C À Hb onds (! [2] Ad irecting-group-based approach for selective remote meta-CÀHf unctionalizations has been pioneered by the group of Yu [3] and subsequently extended by the groups of Tana nd Li, as well as our group.…”

“…[1] In all these cases,DGs have been identified as the crucial component for ortho-CÀHa ctivation and predictable transformation relies on formation of either af ive or six membered metallacycle intermediate.I ns tark contrast, only al imited number of methods are available for selective meta-functionalization of arenes. [3,4] Analogous to the Pd II /Pd 0 pathways,t he Rh III /Rh I cycles are commonly present in oxidative coupling reactions.I n addition, af ew similar aspects have been observed for both palladium-and rhodium-catalyzed oxidative coupling reactions: [5] 1) C À Hactivation is well known for C(sp 2 ) À Hbonds, 2) formation of MÀCbonds by CÀHactivation are generated through chelation assistance,3 )scope with respect to the coupling partners is limited to unsaturated molecules such as alkenes and alkynes.H owever,r hodium-catalyzed oxidative C À Hfunctionalizations have been less explored in contrast to palladium-catalyzed reactions.R hodium catalysis would be highly desirable if it can provide better reaction scope and selectivity.I ndeed, ortho-selective functionalization of arene C À Hb onds have been successfully explored with rhodium. [4] In these cases,anitrilecontaining template assists the palladium center to activate remote meta-C À Hb onds (!…”